Simić T, Mimić-Oka J, Sindjić M
Institute of Biochemistry, Belgrade.
Srp Arh Celok Lek. 1996;124 Suppl 1:45-7.
Recent data have shown the protective effect of thiol groups on the progression of adriamycin-induced experimental nephropathy, in which reactive oxygen metabolites have been postulated to play an important role. To gain greater insight in the role of glutathione (GSH) in adriamycin-induced nephrosis, we studied changes in reduced GSH level and its associated enzymes in kidney tissue of rats undergoing chronic renal failure produced by i.v. infections of adriamycin (2 x 2 mg/kg b.w.). Kidney damage was characterized by increases in relative kidney weight and BUN levels. The results obtained revealed a 15% drop in renal GSH level in adriamycin-treated animals associated by a similar decrease in the gamma-glutamylcysteine synthetase activity. The activities of kidney glutathione reductase (GR) and glutathione peroxiase (GSH-Px) which are critical constituents of GSH-redox cycle, were significantly decreased (23 an 26%, respectively) in response to adriamycin treatment. Rat kidney glutathione-S transferase and gamma-glutamyl transpeptidase activities were not affected in adriamycin induced nephrosis. We propose that the impairment of renal antioxidant defense, characterized by combined drop in GSH, GR and GSH-Px levels, could permit enhanced free radical induced kidney damage in adriamycin-induced nephropathy.
近期数据显示,巯基对阿霉素诱导的实验性肾病进展具有保护作用,其中活性氧代谢产物被认为起重要作用。为更深入了解谷胱甘肽(GSH)在阿霉素诱导的肾病中的作用,我们研究了经静脉注射阿霉素(2×2毫克/千克体重)导致慢性肾衰竭的大鼠肾组织中还原型GSH水平及其相关酶的变化。肾损伤的特征是相对肾重量和血尿素氮水平升高。所得结果显示,阿霉素处理的动物肾GSH水平下降了15%,同时γ-谷氨酰半胱氨酸合成酶活性也有类似程度的降低。作为GSH-氧化还原循环关键成分的肾谷胱甘肽还原酶(GR)和谷胱甘肽过氧化物酶(GSH-Px)的活性,在阿霉素处理后显著降低(分别降低23%和26%)。阿霉素诱导的肾病对大鼠肾谷胱甘肽-S转移酶和γ-谷氨酰转肽酶活性没有影响。我们认为,以GSH、GR和GSH-Px水平共同下降为特征的肾抗氧化防御受损,可能会使阿霉素诱导的肾病中自由基诱导的肾损伤加剧。